Hepatitis B is a disease which is induced by a hepatitis B virus (hereinafter, referred to as "HBV") and includes immunologically and clinically very serious problems for which there is not effective therapeutic method. This disease has been observed worldwide, particularly in Asian and African areas, and hence, it has been desired to find an effective prophylactic and therapeutic method therefor.
HBV is a spherical virus having a diameter of 42 nm and consists of a surface and a core which have separate antigenicity and are called HBs antigen and HBc antigen, respectively. It is also known that there is another antigen of HBV, i.e. HBe antigen reported by Magnius et al. [cf. J. Immunology, 160, 1017 (1972)].
For prophylaxis of this disease, it is very important to discover the infection with HBV at an early stage. For the diagnosis of the infection with HBV, there are utilized antigen-antibody systems such as HBs antigenantibody, HBc antigen-antibody and HBe antigen-antibody. Among these, except HBc antigen which is almost not present in blood flow, five antigens and antibodies can be measured by immunological measurement such as passive hemagglutination (hereinafter, referred to "PHA"), reverse-passive hemagglutination (hereinafter, referred to "rPHA"), enzyme immunoassay (hereinafter, referred to "EIA") and radioimmunoassay (hereinafter, referred to "RIA"). In particular, HBe antigen is very important as an index for diagnosis of infection with HBV. It is known that HBe is a derivative of a HBc antigen protein and hence is dominated by the HBc gene. That is, when the product is associated to form a completely spherical particle, it shows an antigenicity as HBc, but on the other hand, when the product is dissociated, it shows other antigenicity than HBe [cf. KanTan-Sui (Liver-Gall-Pancreas), 10, 7-13 (1985)]. It is also known that HBc antibody shows, in blood, some behavior parallel to the amount of HBc antigen which is the main body of HBV within the liver. It is very important to measure HBc antibody in order to know whether HBV increasing or decreasing within the liver, because it can not be detected by the measurement of HBs antigen, HBe antigen or HBe antibody.
For the measurement of HBc antibody, a pure HBc antigen is necessary. However, HBV antigen is not present in blood flow as HBc antigen per se and HBc antigen must be isolated from human liver. Besides, it is very difficult to isolate from human liver, and the isolation is accompanied with some danger of infection. Thus, since the isolation of HBc antigen is restricted, the human-origin HBc antigen has merely been used in research laboratories for measuring HBc antibody.